The main goal of this proposal is to establish a Center in Neuroscience Research designed to bring a variety of genetic approaches, including transgenic animals and gene transfer methodology, to bear on the study of how individual genes control behavior and learning in mammals. We propose to probe how changes produced by individual genes are reflected in behavior by examining the development of neuronal circuitry, the circuitry's signaling and plastic capabilities, and the circuitry's ability to be modified by experience. To accomplish this goal, the faculty of nine different laboratories at Columbia P&S will focus their efforts on six different projects involving three major themes. A. Neuronal Differentiation and Development: Project 1: Control of Neural Cell Identity and Pattern by Growth Factors. Project 2: Functions of Growth Factors and their Tyrosine Kinase Receptors in Mammalian Neural Development. B. Signal Transduction, Learning and Memory: Project 3: Initial Steps in the Induction of LTP and Spatial Memory: The Molecular Physiology of the NMDA Receptor. Project 4: Later Steps in the Induction of LTP and Spatial Memory: Activation of Second Messengers. C. The Regulation of Transmitter Release by Learning. Project 5: The Retrograde Signal and the Facilitation of Transmitter Release in LTP. Project 6: Role of Presynaptic Proteins in Transmitter Release and Synaptic Plasticity.